Clinical Trial to Determine Tolerable Dosis of Vorinostat in Patients With Mild Alzheimer Disease (VostatAD01)
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|ClinicalTrials.gov Identifier: NCT03056495|
Recruitment Status : Recruiting
First Posted : February 17, 2017
Last Update Posted : November 9, 2017
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer Disease||Drug: N-hydroxy-N'-phenyl-octanediamide (Vorinostat)||Phase 1|
The MTD of Vorinostat in the treatment of Alzheimer's patients is to be determined by using an open, non-randomized, multicentric dose-finding study with adaptive design. This Clinical Trial will take place in 2 parts.
The first part will be performed as a dose escalation part in cohorts of three subjects. Possible dosages will be: one, two, three or four capsules (100 mg per capsule) once per day. The first cohort receives a dose of 100 mg per day. After the treatment, a Vorinostat-free follow-up phase will take place. For the following cohorts, dose increases, a repetition of the previous dose or a dose reduction are possible.
After the dose escalation with a determination of the MTD, a dosage confirmation is carried out with additional subjects. The subjects are given a dose of Vorinostat of MTD over 4 weeks followed by a Vorinostat-free follow-up phase.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||44 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Multicenter, Open-label Phase Ib Dose-escalation and Dose-confirmational Study for the Tolerability and Safety of N-hydroxy-N'-Phenyl-octanediamide (Vorinostat) in Patients With Mild Alzheimer's Disease|
|Actual Study Start Date :||September 28, 2017|
|Estimated Primary Completion Date :||July 2019|
|Estimated Study Completion Date :||October 2019|
Experimental: Investigational drug
N-hydroxy-N'-phenyl-octanediamide (Vorinostat) capsules once a day, three weeks of treatment; dose escalation with different dosages per cohort; One cohort of three subjects
Drug: N-hydroxy-N'-phenyl-octanediamide (Vorinostat)
N-hydroxy-N'-phenyl-octanediamide capsules once a day, three weeks of treatment; dose escalation with different dosages per cohort; One cohort of three subjects
Other Name: Vorinostat
- Determination of the maximum-tolerated dose (MTD) in elderly subjects during dose escalation [ Time Frame: 12 months ]
A MTD is defined as the highest dose with no > grade 1 toxicity according to Common Toxicity Criteria (CTC).
The dose-limiting toxicity (DLT) is defined as the dose, which leads with a 30% chance of toxicity to CTC Grade 2 or higher and / or leads to corrected QT interval (QTc)≥480ms and/or increase of QTc >= 50ms compared to baseline
- Incidence of treatment - Emergent Adverse Events (Safety) [ Time Frame: during dose escalation and during 4 weeks treatment with MTD every week ]
The analysis of safety assessments will include the following data collected for each subject:
- Adverse Events (AEs) in the context of Drug Exposure (days)
- Quantification of Vorinostat concentration in blood - pharmacokinetics [ Time Frame: d21 by 4 weeks treatment with MTD ]
Blood and plasma area under the concentration time curve of Vorinostat from time zero to 8 hours postdose.
The pharmacokinetic study will investigate the correlation between dose administered and concentration of Vorinostat in blood.
- association of alterations in the genome-wide transcriptome profile with the dose administered, toxicity and treatment response - pharmacodynamics [ Time Frame: d21 by 4 weeks treatment with MTD ]The genome-wide transcriptome profile will be determined as a pharmacodynamic surrogate parameter. Alterations between baseline and after dose administered will be compared. The pharmacodynamic study will investigate the correlation between dose administered, alterations in the genome-wide transcriptome profile as well as treatment responses (memory performance) and toxicities.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03056495
|Contact: Sandra Kuhs, Dr. rer. email@example.com|
|German Center for Neurodegenerative Diseases||Recruiting|
|Bonn, Germany, 53127|
|Contact: Anja Schneider, Prof. Dr. med. 0049-228-287-1137 firstname.lastname@example.org|
|University Medical Center Göttingen, Department of Psychiatry and Psychotherapy||Recruiting|
|Göttingen, Germany, 37075|
|Contact: Jens Wiltfang, Prof. Dr. med. 0049-551-3966601 email@example.com|